A centre midfielder, Blasi made his Serie A debut for A.S. Roma in a match against Piacenza on 22 January 2000. he also played for Lecce at Serie B before returned to Roma. In mid-2000 he was signed by Perugia at (first in co-ownership deal for a peppercorn of 1 million Italian lire; €516). Which he played 46 Serie A matches. In June 2001, he was signed permanently for 18 billion lire (€9.296 million)), however, in terms of the signing of Giuseppe Cattivera also for 18 billion lire.
In July 2002, he was signed by Juventus, and loaned back to Perugia in the first season.
In the next season, due to the injury of Gianluca Pessotto, he played as right-back. Due to the arrival of Patrick Vieira, he is lack of first team chance at midfield, in although awarded a new contract until 2009. He played 6 start.
Along with former team-mate Marcelo Zalayeta, Blasi was sold to newly promoted Serie A team Napoli for €1.4M and €2.45 million respectively in co-ownership deal. He signed a 5-year contract. In June 2008 Napoli bought the remain half for €2.6 million.
^"Ufficiale l'arrivo di Manuele Blasi". ACF Fiorentina (in Italian). 21 June 2006. Archived from the original on 30 June 2006. Retrieved 30 June 2006. "La Fiorentina comunica di aver acquisito a titolo temporaneo con diritto di riscatto le prestazioni sportive del centrocampista Manuele Blasi, classe 1980, dalla Juventus FC."